Normal mature blood cells exhibit little proliferative activity and have a finite life span; the cells must, therefore, be replaced by a continuous process of recruitment and differentiation which is tightly regulated and is accompanied by a loss of proliferative capacity. Leukemia cells do not respond to the normal growth controls and regulators of differentiation and, as a result, are characterized by unrestrained growth. In malignant cells which can be induced to undergo differentiation, the process is often accompanied by a loss of neoplastic growth properties. These studies will focus on determining whether the induction of differentiation in leukemia cells will reduce their leukemogenicity as a potential mode of therapy for the disease. We will use Abelson murine leukemia virus induced leukemia cells as a model because of their similarities to the human acute lymphocytic leukemias. Abelson virus efficiently transforms hemopoietic cells in vitro and in vivo, and the leukemia cells share many characteristics with the non-T, non-B human lymphoid leukemias. The potential for differentiation of Abelson leukemia cells will be systematically tested using agents which are known to influence differentiation of murine hemopoietic cells and monitored using the differentiation markers available for mouse lymphocytes. The effects of inducing differentiation on leukemogenicity and virus systems will be tested.